Search

Aim. Study of the association of polymorphic variants of CYP2C19 (G681A), P2RY12 (H1/H2), ITGB3 (T1565C), ITGA2 (C807T), eNOS3 (T786C) genes with high residual platelet reactivity (HRPR) to clopidogrel and acetylsalicylic acid (ASA) at different terms of myocardial infarction (MI).Material and methods. The study included 400 patients with MI aged 31-74 years, 317 (79,3%) men and 83 (20,7%) women. Platelet aggregation performed on days 1-2, 12-14 and 28-30 of MI, and genotyping by the polymerase chain reaction were analyzed using the STATISTICA 10.0 program.Results. Differences were found in ADP-test 1-3 depending on the CYP2C19 (G681A) polymorphism, ADP-test 1 depending on the P2RY12 (H1/H2) polymorphism, ADP-test 2 depending on the ITGB3 (T1565C) polymorphism, ASPI-test 1 depending on the eNOS (T786C) polymorphism. The risk of HRPR to clopidogrel is higher in 681A CYP2C19 allele carriers compared to the G681 carriers throughout the entire observation period: initially odds ratio (OR) of 1,8 (1,14-2,88), p=0,012, on days 12-14 of MI, OR of 1,7 (1,08-2,68), p=0,023 and on days 28-30 of MI, OR of 2,3 (1,42-3,81), p=0,0008. The risk of HRPR to clopidogrel is higher in AA CYP2C19 genotype carriers compared to GG genotype carriers, on days 1-2 of MI (OR 6,5 (1,16-36,4), p=0,033), on days 28-30 of MI (OR 7,8 (1,26-48,0), p=0,027). The risk of HRPR to clopidogrel on days 1-2 of MI is higher in H2 P2RY12 locus carriers compared to H1 locus carriers (OR 1,5 (1,02-2,22), p=0,039). The risk of HRPR to ASA on days 1-2 of MI is higher in the 786C eNOS3 allele carriers compared to T786 allele carriers (OR 1,4 (1,02-1,96), p=0,036). Carriers of haplotypes of minor alleles of CYP2C19 + ITGA2 + P2RY12 + eNOS genes (OR 3,9 (1,13-13,65), p=0,032) and CYP2C19 + ITGA2 + eNOS genes (OR 5,1 (1,7214,96), p=0,0032) have higher risk of HRPR to dual antiplatelet therapy (DAPT) on days 28-30 of MI compared to the rest of patients.Conclusion. The association of HRPR to clopidogrel with the CYP2C19 (G681A) polymorphism was found during the entire observation period, with the P2RY12 (H1/H2) polymorphism on days 1-2 of MI, with the ITGB3 (T1565C) polymorphism on days 10-12 of MI. The association of HRPR to ASA with eNOS (T786C) polymorphism was found on days 1-2 of MI. Minor allele haplotypes of the CYP2C19 + ITGA2 + P2RY12 + eNOS genes and CYP2C19 + ITGA2 + eNOS genes were associated with a higher risk of developing HRPR to DAPT on days 28-30 of MI.

Aim. To identify and rank factors predisposing to angina relapse in Buryat patients who underwent percutaneous intervention for acute coronary syndrome.Material and methods. The study included 142 Buryat patients who underwent coronary stenting for acute coronary syndrome. All patients received clopidogrel. The CYP2C19*2 and CYP2C19*3 alleles were determined. Efficacy endpoints were assessed according to the Academic Research Consortium-2 criteria. Laboratory parameters and concomitant omeprazole therapy were assessed.Results. This study examined in detail a group of patients with short-term angina relapse without formal signs of unstable angina. A logistic regression model was obtained that makes it possible to identify and rank independent risk factors for recurrent angina in Buryat patients. Risk factors were ranked as follows: carriage of CYP2C19*2 and/or CYP2C19*3 alleles (coefficient b1=3,489, 95% confidence interval (CI) (3,096-346,213)), treatment with omeprazole (b2=2,816, 95% CI (2,745-101,616)), male sex (b3=2,749, 95% CI (1,425-163,458)) and blood glucose level (b4=0,354, 95% CI (1,141-1,779)).Conclusion. Thus, angina pain relapse in Buryat patients is facilitated by signs significant for recurrent myocardial infarction. This study suggests that patients with recurrent angina pain without electrocardiographic deterioration and biomarker elevation may require more careful personalization of therapy.

CYP2C and CYP3A cytochromes are induced by a variety of compounds and affect the pharmacokinetics and pharmacodynamics of a large number of drugs. Currently, the possibility of using copper coordination compounds in antitumor therapy is being actively studied. Evaluation of potential interactions between new molecules and P450 cytochromes is necessary at an early stage of drug design.The aim. To study the modulating effect of Cu(II) complexes with enamine and tetrazole derivatives on CYP2C9, CYP2C19 and CYP3A4 and their cytotoxic and antiproliferative properties on normal human lung fibroblasts MRC-5 and a 3D model of hepatocellular carcinoma HepG2.Materials and methods. Cytotoxic and antiproliferative activities of copper(II) complexes – [CuL2] (1), [Cu2(bipy)2(PT)4] (2), [Cu2(phen)2(PT)4] (3), {[Cu(phen)(MT)2]∙H2O}n (4) (L – anion of 2-anilinomethylidene-5,5-dimethylcyclohexane-1,3-dione; PT – 5-phenyltetrazolate anion; MT – 5-methyltetrazolate anion; bipy – 2,2’-bipyridine; phen – 1,10-phenanthroline) – were examined in 2D and 3D models using fluorescence-based phenotypic screening. The modulating effect on CYP2C9, CYP2C19 and CYP3A4 was studied using fluorescence-based targeted screening. The results of CYP3A4 expression were confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR).Results. Complex (1) increases the CYP3A4 expression and does not affect CYP2C9 and CYP2C19 expression. Complex (2) has no modulating effect on CYP2C and CYP3A. Complexes with 1,10-phenatrolin (3) and (4) induce CYP3A4, inhibit CYP2C9 and do not affect CYP2C19 expression. All compounds have a dose-dependent cytotoxic effect on HepG2 and MRC-5: the compound with 5-methyltetrazolate anion (4) has the same effect on cell lines, compounds with 5-phenyltetrazolate anion (2) and (3) have selective effect. Complexes with 1,10-phenatrolin are effective on both 2D and 3D models.Conclusion. The [Cu2(phen)2(FT)4] complex (3) can be used as a basis for creating an antitumor compound, but further modification of the structure is required to increase the selectivity to tumor cells.

Introduction. In modern systematic reviews, there is a point of view that CYP2C19 polymorphism affects the results of treatment of peptic ulcer, erosive esophagitis and eradication of Helicobacter pylori.Оbjective. To evaluate the effect of CYP2C19 polymorphism on the effectiveness of treatment with rabeprazole at a dose of 20 mg once a day in patients with GERD during 2 and 4 weeks of treatment.Materials and methods. In total, the study included 75 patients with GERD (36 men and 39 women, mean age 41.7 ± 1.5 years). A clinical examination with the completion of standard questionnaires took place during three visits: before the start of treatment, after 2 and after 4 weeks of therapy. Esophagogastroduodenoscopy was performed in all patients before treatment and in patients with esophagitis after 4 weeks of therapy. All patients received rabeprazole at a dose of 20 mg once a day. Genotyping of single nucleotide polymorphisms of CYP2C19 metabolizer genes was carried out by real-time polymerase chain reaction. Ultrarapid, rapid, normal, intermediate and poor CYP2C19 metabolizers have been isolated.Results. Of the 75 patients examined, 8.0% of patients were ultrarapid metabolizers, 30.7% of people were rapid, 49.3% of individuals were normal, 10.7% of persons were intermediate, and 1.3% of patients were poor CYP2C19 metabolizers. Response after 4 weeks of treatment with rabeprazole 20 mg once daily was 94.4% for NERD and 90.5% for erosive esophagitis. In ultrarapid and rapid metabolizers of CYP2C19, a complete response to rabeprazole therapy was registered in 81.3% of NERD patients and in 84.6% of patients with erosive esophagitis.Conclusion. Based on the results of the study, we obtained high efficacy of Razo® at a dose of 20 mg 1 time per day for the treatment of GERD in a group of patients with a predominance of rapid and normal metabolizers of CYP2C19.

Introduction. A treatment for LFR for many years, the superiority of PPIs over placebos is still controversial. Of particular clinical importance is the metabolic rate of PPIs in hepatocytes using the cytochrome P450 system with the participation of the isoenzyme CYP2C19 and partially CYP3A4Аim. We set a goal to study the efficacy of omeprazole 20 mg in the treatment of LFR symptoms without esophageal syndrome in patients with gastroesophageal reflux (GERD), depending on the polymorphism of the CYP2C19 genotype.Мaterials and мethods. After the exclusion criteria, 100 people took part in the study, 94 people completed the study.Results. According to the results, 26.6% of patients in the study group (residents of the Moscow region) with LFR symptoms without esophageal syndrome belong to fast metabolizers of CYP2C19, 4.2% to ultrafast metabolizers, 52.1% to normal metabolizers, 16% to intermediate metabolizers and 1.1% to slow CYP2C19.Conclusions. In patients with a rapid metabolism, within 1 month after discontinuation of omeprazole, it is necessary to increase the amount of omeprazole 20 mg intake up to 2 times a day in the morning and in the evening and reduce the duration of treatment to 6 weeks.

Statins are efficacious lipid-lowering drugs used for prevention of cardiovascular complications in patients with high blood cholesterol. The efficacy and safety of this group of drugs is largely determined by genetic factors. The aim of the study was to analyse the effect of gene polymorphisms on the efficacy and safety of atorvastatin in patients undergoing hospital treatment. Materials and methods. The authors carried out a retrospective study of the medical records of 76 hospital patients who were prescribed atorvastatin for confirmed hyperlipidemia. All the patient records contained the results of genotyping of single nucleotide polymorphisms that presumably affect the pharmacokinetics and pharmacodynamics of statins. Results. The analysis of literature data suggested that the pharmacological response and safety of statins could be affected by polymorphisms of the following genes: SLCO1B1, ABCB1, CYP2C9, and CYP2C19. The study showed that atorvastatin had high efficacy in the carriers of the 3435C allele of the ABCB1 gene and in the carriers of the CYP2C19*2 allele of the CYP2C19 gene. The patients carrying ABCB1 genotypes demonstrated a tendency to increasing levels of low-density lipoproteins and total cholesterol in the following order: 3435СС → 3435СТ → 3435ТТ. The only adverse reaction of atorvastatin in the patient groups was an increase in the activity of hepatic transaminases, however, no connection with the studied gene polymorphisms was observed. Conclusions. The study of the effect of gene polymorphisms on the efficacy and safety of statins will be continued to obtain statistically valid confirmation of the observed trends in a much larger group of patients.

The aim of our study was to study the relationship between the CYP2C19 genetic polymorphism and the efficacy and safety of diazepam in patients with alcohol withdrawal syndrome in order to develop algorithms for optimizing the therapy of diazepam to reduce the risk of dose-dependent adverse drug reactions and pharmacoresistance.Materials and methods. The study was conducted on 30 Russian male patients suffering from alcohol withdrawal syndrome. For the treatment of anxiety, fear and emotional tension, patients received diazepam in injections at a dosage of 30,0 mg / day for 5 days. Genotyping was performed by real-time polymerase chain reaction with allele-specific hybridization. The efficacy and safety assessment was performed using psychometric scales and scales for assessing the severity of adverse drug reactions: the Clinical Institute Withdrawal Assessment for Alcohol scale, the visual-analogue scale of the craving for alcohol, and the side-effect scale.Results. Based on the results of the study, we revealed the differences in the efficacy of therapy in patients with different CYP2C19 -806C>T genotypes: (CC) –12,0 [–15,0; –8,0], (CT + TT) –7.0 [–14,0; –5,0], p = 0,001. The scores on the UKU scale, which was used to evaluate the safety of therapy, were also different: (CC) 8,0 [6,0; 12,0], (CT + TT) 6,0 [6,0; 12,0], p = 0,006.Conclusion. The relationships between the CYP2C19 genetic polymorphism and the efficacy and safety of diazepam were demonstrated. This should be taken into consideration when prescribing this drug to such patients in order to reduce the risk of adverse drug reactions and pharmacoresistance.

Aim. To evaluate an association of genetic polymorphisms CYP2C19, MDR1, and IL-1β on the eradication rate by 10-day modified therapy in patients with H. pylori - associated diseases. Materials and methods. In this study was conducted a prospective, randomized trial, included 89 patients with H. pylori - associated diseases. They were divided into 2 groups depending on therapy: clarithromycin 500 mg, b.i.d., amoxicillin 1000 mg, b.i.d., bismuth subcitrate 240 mg, b.i.d. rabeprazole 20 mg or 40 mg, b.i.d. for 10 days. All subjects underwent pharmacogenetic testing of CYP2C19, MDR1, and IL-1β. Results and discussion. Per - protocol (PP) eradication rates in group with rabeprazole 40 mg were 97.6% (41/42; 95% CI 87.7-99.6), in group with rabeprazole 20 mg were 82.1% (32/39; 95% CI 67.3-91.0). Intention - to - treat analysis in group with rabeprazole 40 mg eradication rates were 89.1% (41/46; 95% CI 77.0-95.3), in group with standard dose rabeprazole - 74.4% (32/43; 95% CI 59.8-85.1). No significant differences in eradication rates between the groups of ultrarapid, rapid, normal and intermediate CYP2C19 metabolizers (PP: 93.5%/90.3%/84.6% respectively; χ2=0.87, p=0.65). Eradication rates in group with IL-1β CC genotype there was no difference among the IL-1β CT and TT genotype groups (PP: 92.9%/85.7%/94.7% respectively; χ2=1.34; p=0.51). The cure rate among MDR1 TT genotype was significantly lower than among subjects in the MDR1 CC/CT genotype groups (PP: 76.2% vs 96.3%: χ2=5.04; p=0.025; OR=8.13). Conclusion. Ten - day modified triple therapy with high dose rabeprazole significantly high eradication rates in patients with H. pylori - associated diseases. Independent factor for treatment failure is MDR1 CC/CT genotype status.

The considered clinical case of combination of multifocal atherosclerotic vascular lesion with type 2 diabetes mellitus and liver fibrosis demonstrates a combination of polyvalent risk factors for resistance to antiplatelet therapy with clopidogrel. The decrease in the effectiveness of prolonged therapy with P2Y12 inhibitor was clinically manifested by repeated thrombotic events and was confirmed by laboratorial VerifyNow P2Y12 Assay test system as a low percentage of inhibition of ADP-induced platelet aggregation. We established probable genetic predictors of the decrease in the effectiveness of antiplatelet therapy in this patient, namely, the carriage of polymorphic markers of the ABCB1 CT, CES1 CA and CYP3A4*22 CT genes that determine the decrease in absorption, excessive hydrolysis of the drug and reduced activity of isoenzymes and transporters, that leads to disorders of active clopidogrel metabolite formation. A potential contribution of hepatic dysfunction to reduction in antiaggregant effect of P2Y12 inhibitor was demonstrated. Variant of drug interaction of clopidogrel and an inhibitor/substrate of P450 CYP2C19 – omeprazole, accompanied by a decrease in the effectiveness of antiplatelet therapy, was also considered.

Aim. To assess the clinical, biochemical, and genetic risk factors for the development of hepatocyte cytolysis syndrome in patients with a combination of fatty liver disease and recrudescence of chronic cardiovascular pathology.Material and methods. The study included 74 patients with chronic cardiovascular disease (coronary heart disease, chronic heart failure, hypertension) treated in the cardiology department of the Central Clinical Hospital of the Siberian Branch of Russian Academy of Sciences with a normal baseline transaminase level (AST and ALT); 12 of them have increasing of transaminase level on 10-12 days. All patients underwent therapeutic and diagnostic procedures in accordance with the medical standards in Russian Federation. Genotyping of polymorphic loci of the genes of the cytochrome P450 family was carried out using real-time polymerase chain reaction (PCR).Results. There was no significant correlation between cytolysis syndrome and phenotypic characteristics: gender, age, body mass index. A positive correlation of fatty liver disease with abdominal obesity and body mass index was confirmed. There was no significant correlation between cytolysis syndrome and clinical and biochemical risk factors: comorbidity and lipid profile. The presence of minor minor allele of cytochrome P-450 — CYP2C9, CYP2D6, CYP2C19 genes in a patient with fatty liver disease increases the risk of cytolysis syndrome during CVD therapy.Conclusion. Pharmacogenetic testing of polymorphic variants of cytochrome P-450 — CYP2C9, CYP2D6, CYP2C19 genes is advisable to recommend to patients with cardiovascular diseases and high-risk of liver disorders for a personalized approach to therapy.

Aim. To study the use of CYP2C19 pharmacogenetic testing (PhGT) for personalization of antiplatelet therapy in patients with acute coronary syndrome (ACS) in routine practice.Material and methods. The study included 103 patients with ACS without indications for long-term anticoagulant therapy, which underwent CYP2C19 PhGT aimed at antiplatelet therapy personalization.Results. According to CYP2C19 genotyping the GG, GA, AA allelic variants were detected. CYP2C19*2 PhGT revealed that genotypes GG, GA and AA were carried by 76 (73.8%), 23 (22.3%) and 4 (3.9%) patients, respectively. Initially 86 (83.5%) patients received clopidogrel, 17 (16.5%) – ticagrelor. After therapy correction based on genotype GA and AA, the proportion of ticagrelor receiving patients increased from 25.9% to 55.5% (relative risk=0.172; 95% confidence interval 0.075-0.396; p

In current clinical practice, there is no optimal empirical therapy for Helicobacter pylori (H. pylori) infection and there is a progressive decrease in the efficiency of classical eradication therapy (ET) regimens. The variability in the efficiency of ET in a specific patient is largely due to the heterogeneous molecular genetic mechanisms underlying the resistance of the microorganism to the components of the treatment regimens. The basis of the mechanisms for antibiotic resistance in H. pylori is mainly the point mutations in some genes, which determine alterations in the mechanisms of action of drugs, such as clarithromycin (domain V of 23S rRNA), metronidazole (rdxA, frxA), amoxicillin (pbp1A), tetracycline (16S rRNA), and levofloxacin (gyrA). The predictors of resistance to ET are also the CagA-negative status of the microorganism and the presence of the vacA s2 allele. There are a number of host genetic determinants (the CYP2C19 genotype (*1/*1, *1/*17, *17/*17) and the MDR1 3435 T/T genotype (in an Asian population)) that reduce the efficiency of ET, by altering the pharmacokinetics of proton pump inhibitors. In addition, the IL-1β-511 C/C polymorphism that affects gastric acid secretion is a predictor of the inefficiency of ET.

Tamoxifen is a selective modulator of estrogen receptors and is widely used in receptor-a-positive breast cancer treatment. Adjuvant tamoxifen treatment substantially reduces breast cancer relapse and mortality rates. However, high interindividual variability in response is observed. One of the causes of this variability may be genetic polymorphisms of the cytochrome P450 (CYP) enzymes, which are responsible for the formation of tamoxifen active metabolites. Polymorphisms of genes encoding the enzymes with decreased or absent activity could be associated with lower tamoxifen active metabolites concentration in serum and consequently reduce the effectiveness of treatment. Pharmacogenetic approach is a promising tool of personalized medicine and may help personolize pharmacotherapy of breast cancer in the future. Throughout this review we analyze the up-to-date information on the influence of the gene CYP2C19 polymorphisms that they have on pharmacokinetic and pharmacodynamic of tamoxifen.

Актуальность. У части пациентов наблюдаются изменения активности клопидогрела за счет полиморфных вариантов rs4244285(*2), rs4986893 (*3), rs12248560 (*17) в гене цитохрома CYP2C19, влияющих на метаболизм. Также есть данные о снижении эффективности клопидогрела у лиц, имеющих генотип Т/Т в rs2305948 гена VEGFR-2. Тем не менее этот препарат используется в России наиболее широко в силу доступности и наличия дженериков. Цель. Оценить распространенность полиморфных вариантов гена CYP2C19: rs4244285(*2), rs4986893 (*3), rs12248560 (*17) и VEGFR-2 rs2305948, а также факторов сердечно-сосудистого риска у пациентов бурятской национальности, подвергшихся стентированию коронарных сосудов по поводу острого коронарного синдрома. Методы. В исследование включены 113 пациентов бурятской национальности, по- ступивших по экстренным показаниям для стентирования коронарных сосудов по поводу острого коронарного синдрома. Пациенты стратифицированы по носительству аллелей CYP2С19*2, CYP2C19*3, CYP2C19*17, и VEGFR-2 rs2305948. Всем пациентам определены следующие лабораторные показатели: глюкоза крови, липидный спектр, креатинин, скорость клубочковой фильтрации, оценена выраженность ате- росклероза коронарных сосудов. Результаты. Определены частоты встречаемости генотипов по данным аллелям. Определены частоты встречаемости гаплотипов (CYP2С19*2, *3, *17). Обнаружена ассоциация между носительством аллеля дикого типа VEGFR-2 rs2305948 и снижением скорости клубочковой фильтрации менее 60 мл/мин/1,73 м2 (χ² = 4,185, р = 0,032), с повышением артериального давления в анамнезе (χ² = 12,593, р = 0,001). Для мужчин выявлена положительная корреляция аллеля С/С VEGFR-2 rs2305948 с числом значимых стенозов коронарных сосудов (R = 0,227, р

Platelets play an important role in the pathogenesis of atherosclerosis. They are involved in atherosclerosis progression and thrombotic complications. That is why antiplatelet therapy is a necessary element of these complications prevention in patients with coronary heart disease. One of the most commonly used antiplatelet agents all over the world is clopidogrel, R2Y12-receptor blocker. It is shown that clopidogrel has insufficient effect in some patients, ie they are resistant to clopidogrel. Genetic causes of resistance to clopidogrel are considered in this review. It is shown that genetic factors related to the metabolism of clopidogrel play an important role in the resistance development. Allel variants of the gene cytochrome CYP2C19 are the main among them. The role of other genes is less studied.

Purpose: the personification approach to the choice of antisecretory drugs in chronic gastroduodenitis, gastroesophagealreflux disease in children.Materials and methods: The study involved 70 children (12-14 years) with chronic inflammatory diseases of the upper digestive tract (WOCAT) (gastroesophageal reflux disease (GERD) in conjunction with chronic gastroduodenitis (CGD)). All children performed esophagogastroduodenoscopy (machine Olympus) with biopsy mucosa (CO) of the distal esophagus, gastric antrum, duodenum and molecular genetic research aimed at identifying gene polymorphism CYP2C19 * 2.Results: 50.2% of children surveyed were identified, rapid metabolizers (RM), while 28.4% of intermediate metabolizers (PM) of proton pump inhibitors (PPIs), while slow metabolizers (SM) IPP in 21.4% of cases .Conclusion: the continuing high activity of gastritis after standard therapy in children with RM/ PM IPP suggests the need for a personalized approach to the choice of antisecretory therapy based on gene polymorphism CYP2C19*2.Personalized approach to treatment of chronicinflammatory diseases of the upper gastrointestinaltract in children with CYP2C19 polymorphismaccount

Antiplatelet therapy is one of the most importance in therapy of patients with injured coronary, cerebral and peripheral arteries. The standard of acute coronary syndrome patients treatment is double antiplatelet therapy: acetylsalicylic acid with P2Y12receptor blocker. Some distinguished genetic specifics might lead to the development of resistance to antiplatelet therapy with further thrombotic complications. Current review focuses on the pharmacogenetic specifics of patients than lead clopidogrel resistance.

The clinical significance of CYP2C19 genetic polymorphism, associated with the violation of the formation of the active clopidogrel metabolite, for efficacy and safety of this drug in cardiology practice is discussed. Approaches to antiplatelet agent choice according to pharmacogenetic CYP2C19 testing, as well as the indications for this approach use in clinical practice are presented. Consideration of these testing results should increase the efficacy and safety of antiplatelet treatment.

The aim of review. To summarize and analyze main causative factors determining inefficacy of modern algorithms of antihelicobacter therapy.Key points. Efficacy of eradication therapy (ET) can depend on a lot of factors which generally can be divided in three main groups in relation to origin: factors determined by microorganism (bacteria); factors determined by macroorganism (patient); the factors determined by doctor. Hence, in clinical practice cases a single patient may have combination of several independent factors determining failure of provided treatment.Conclusion. Efficacy ET depends upon wide spectrum of heterogeneous mechanisms. For the present moment, the primary factor determining inefficacy of treatment, is increase of H. pylori antibiotic resistance to the basic drugs, applied in modes of the first line of ET.

The targets of application of antiaggregant therapy by clopidogrel and the factors that influence its outcome were presented, in this review. Special attention was given to the application of personalized, approach for the optimization of clopidogrel therapy. The data of clinical investigations were discussed.

The prevalence of genotypes and alleles of polymorphous locus 681G>A of CYP2C19 gene in Russian population of Eastern Siberia. We conducted comparative analysis of response characteristics with previous data of other world's populations. Genotyping was conducted using PCR method. Statistical processing was performed using «Hardy - Weinberg equilibrium calculator» and STATISTICA 8.0. Significant differences of prevalence of alleles of studied polymorphous locus between researched population and data of other researchers were discovered.

Aim: To evaluate an association of genetic polymorphisms CYP2C19, MDR1, and IL-1β on the eradication rate by 10-day modified therapy in patients with H. pylori - associated diseases., Materials and Methods: In this study was conducted a prospective, randomized trial, included 89 patients with H. pylori - associated diseases. They were divided into 2 groups depending on therapy: clarithromycin 500 mg, b.i.d., amoxicillin 1000 mg, b.i.d., bismuth subcitrate 240 mg, b.i.d. rabeprazole 20 mg or 40 mg, b.i.d. for 10 days. All subjects underwent pharmacogenetic testing of CYP2C19, MDR1, and IL-1β., Results and Discussion: Per - protocol (PP) eradication rates in group with rabeprazole 40 mg were 97.6% (41/42; 95% CI 87.7-99.6), in group with rabeprazole 20 mg were 82.1% (32/39; 95% CI 67.3-91.0). Intention - to - treat analysis in group with rabeprazole 40 mg eradication rates were 89.1% (41/46; 95% CI 77.0-95.3), in group with standard dose rabeprazole - 74.4% (32/43; 95% CI 59.8-85.1). No significant differences in eradication rates between the groups of ultrarapid, rapid, normal and intermediate CYP2C19 metabolizers (PP: 93.5%/90.3%/84.6% respectively; χ2=0.87, p=0.65). Eradication rates in group with IL-1β CC genotype there was no difference among the IL-1β CT and TT genotype groups (PP: 92.9%/85.7%/94.7% respectively; χ2=1.34; p=0.51). The cure rate among MDR1 TT genotype was significantly lower than among subjects in the MDR1 CC/CT genotype groups (PP: 76.2% vs 96.3%: χ2=5.04; p=0.025; OR=8.13)., Conclusion: Ten - day modified triple therapy with high dose rabeprazole significantly high eradication rates in patients with H. pylori - associated diseases. Independent factor for treatment failure is MDR1 CC/CT genotype status.